High rates of relapse to drug use after prolonged drug-free periods characterize the behavior of experienced heroin and cocaine users, and of people in dietary treatment who attempt to restrict the intake of high-fat palatable food.[unreadable] [unreadable] The behavioral and neurochemical events that contribute to these high relapse rates, however, are not well understood. Relapse can be induced in human subjects and laboratory animals by reexposure to the drug (or food) previously used, re-exposure to environmental cues paired with drug (or food) self-administration, and by exposure to environmental stressors. We are using an animal model of relapse, a reinstatement model, to study brain systems and neurotransmitters involved in relapse induced by environmental stressors, conditioned drug (or food) cues and drug (or food) re-exposure in rats with a history of heroin, cocaine or palatable high-fat food self-administration. [unreadable] [unreadable] During the last year, we have performed several studies. In studies on the neuronal mechanisms underlying relapse to food seeking, we have been exploring the role of the hypothalamic peptides orexin and MCH, and of dopamine D1-family receptors. In studies on context-induced relapse to heroin seeking, we have been exploring the role of dopamine in different ventral and dorsal striatum areas and also examine neuronal activation in several brain areas (prefrontal cortex, orbitofrontal cortex, amygdala, and hippocampus) after exposure to heroin cues. In studies on the molecular mechanisms underlying the time-dependent increases in the responsiveness to cocaine-associated cues after withdrawal from the drug (a phenomenon termed incubation of cocaine craving), we have been exploring the role of CDNF, a newly discovered growth factor that is important for the survival and function of brain dopamine neurons. We also have initiated parallel studies on another incubation phenomenon termed incubation of fear (time dependent increase in the rat's response to a cue previously paired with an aversive environmental event). We currently explore the role of corticotropin-releasing factor (CRF) and corticosterone in incubation of fear.